NOS3 and hypertensive disorder: APJ exists in a variety of cells such as ECs and VSMCs, and is widely expressed in large blood vessels and the vascular system of various organs.420–423 Apelin/APJ mediates vasodilation primarily by activating the eNOS/NO pathway in ECs.424–426 Clinical studies showed that reduced circulating Apelin was significantly associated with an increased risk of hypertension.427 And in animal studies, peripheral injection of Apelin can cause extensive vasodilation, as well as a decrease in blood pressure.428 Furthermore, Apelin/APJ also interacts with RAAS.